Clinical Review - Bacterial meningitis in children

How to recognise and manage bacterial meningitis as a GP. By Dr Scott Hackett

Rates of Hib meningitis have fallen from 800 to fewer than 20 cases per year (Photograph: SPL)
Rates of Hib meningitis have fallen from 800 to fewer than 20 cases per year (Photograph: SPL)

Section 1: Epidemiology and aetiology

Bacterial meningitis is a potentially life-threatening illness that results from bacterial infection of the meninges.

Acute meningitis (from any cause) is a notifiable disease. Notifications have fallen from more than 2,700 in 1991 to about 900 in 2010.1

Bacteria probably invade the bloodstream via the tonsils and then the meninges by direct haematogenous spread.

Less commonly, they may spread directly from an infected area, such as the sinuses. Patients often have concomitant bacteraemia and may have symptoms and signs of sepsis, especially in meningococcal disease (MCD).

The intense meningeal inflammation, as well as abnormal cerebral circulation (due to local and systemic factors), lead to irritability, reduced levels of consciousness and raised intracranial pressure.

The impact of vaccines
Beyond the neonatal period, the three most common organisms causing acute bacterial meningitis are Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Since the introduction of routine use of conjugate Hib, pneumococcal and meningococcal C vaccines, the incidence of meningitis has decreased.

Hib meningitis used to be the most common meningitis in children in the UK, but since the introduction of the Hib vaccine in 1992 and the booster/catch-up campaign from 2003, rates have fallen from more than 800 to fewer than 20 cases per year.2 Following the introduction of the meningococcal serogroup C conjugate vaccine in 1999, rates of invasive meningococcal C disease including meningitis fell by more than 90%.

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Serogroup B now accounts for 90% of all meningococcal cases in the UK; there are no licensed vaccines in the UK.3

Pneumococcal conjugate vaccines have led to a significant reduction in invasive pneumococcal disease, including meningitis. Despite falling rates, there has been some serotype replacement with non-vaccine serotypes. In 2008, 74% of serotypes were covered and surveillance is continuing.4

Penicillin-resistant Strep pneumoniae is not a major clinical problem in the UK but should be considered if therapy is failing, especially in patients returning from regions where resistance is common.

Bacterial meningitis needs to be separated from other infective causes of meningitis in children, including viral, mycobacterial (TB), fungal and protozoal, as well as encephalitis and non-infective causes, such as Kawasaki disease.

Section 2: Making the diagnosis

In children under two years of age, the classic features of meningitis may not always be present. Most children with non-specific symptoms will not have a significant bacterial infection, including meningitis, but early diagnosis and treatment improves outcome.

Symptoms and signs of meningitis in those aged less than two, and between two and 16 years are detailed in the box below.5

Symptoms and signs of bacterial meningitis in children aged <2 years="" and="" 2-16="" sup="">5
Symptoms Age <2 years="" strong=""> Age 2-16 years
Fever Majority
Length of symptoms Can be acute (1-2 days), insidious (2-5 days) (most common) or fulminant with early shock (most have MCD)
Lethargy/apathy/reduced mental state Majority 
Irritability/listlessness/shrill cry Majority
Poor feeding/anorexia Majority
Vomiting and/or diarrhoea Often present  May be present
Headache Not obvious  Majority
Bulging fontanelle <1 year="" old="" poor="" specificity="" but="" needs="" further="" evaluation="" td="">  N/A
Pallor/shock/poor capillary refill time If systemically unwell or sepsis 
Reduced level of consciousness May be present
Neck stiffness Often absent  Majority unless very unwell
Kernig’s and Brudzinski’s signs* Often absent  Minority
Photophobia Difficult to elicit  Often present
Seizures 20-30% can have seizure
Papilloedema Rare in acute meningitis, suggests another diagnosis 
Cranial nerve palsy Rarely seen; if present, suspect raised intracranial pressure
Rash If bacteraemia or septicaemia, may be blanching,
flea-bitten petechiae or purpura
*Kernig’s sign: knee extension leads to neck pain. Brudzinski’s sign: flexing of hips when flexing patient’s head

Patients with TB meningitis often have a protracted history of headache, weight loss, sweats and fevers. Early diagnosis is difficult unless TB is considered.

Viral encephalitis is often difficult to differentiate from bacterial meningitis, but patients' levels of consciousness are often significantly reduced, more than can be explained by the severity of the illness or circulatory compromise.

Lumbar puncture
Most patients over two years of age should be diagnosed clinically. Acute phase reactants such as CRP, as well as neutrophils, are often elevated in patients with bacterial meningitis, but will not differentiate 100% meningitis from patients with other infections. For a definitive diagnosis, a lumbar puncture (LP) is necessary.

If a diagnosis of meningitis is high on the differential list and the LP is likely to be delayed, parenteral antibiotics should be administered. Early antibiotics will affect culture (CSF culture-positive rates reduced to 10%) but not PCR positivity rates.

Contraindications to performing an LP (some relative) include:

  • Unstable patient with circulatory or respiratory compromise.
  • Widespread or spreading purpura.
  • Signs of raised intracranial pressure, including unequal, dilated or poorly responsive pupils and papilloedema.
  • Reduced levels of consciousness.
  • Focal neurological signs.
  • Abnormal posture or posturing.

A normal CT or MRI does not rule out raised intracranial pressure.

Section 3: Managing the condition

As with all paediatric conditions, treatment for bacterial meningitis initially follows the ABC algorithm, accessing the airway, breathing and circulation.

This is particularly important if the child has a reduced level of consciousness, poor circulation or respiratory distress. IV access and bloods should be taken where meningitis is suspected. Correction of dehydration and poor perfusion is vital, but care needs to be taken to ensure that fluid overload and worsening of cerebral oedema does not occur.


Glass test: if the rash does not fade, urgent advice must be sought (Photograph: SPL)

Antibiotics
Early disease recognition, prompt antibiotics, referral to secondary care and, if needed, liaison with specialist intensive care facilities has significantly improved outcomes.

If access is impossible, IM antibiotics are an option (penicillin or ceftriaxone). As stated in section 2, if meningitis is likely and the LP might be delayed (exact time not defined; if there are signs of circulatory compromise, any delay is unacceptable), IV or IM antibiotics should be administered immediately.

Outside the neonatal period, first-line therapy is generally cefotaxime or ceftriaxone. In primary care, especially if MCD is suspected with or without meningitis, IM penicillin or ceftriaxone is recommended.

In patients who have potential penicillin allergy, cefotaxime or ceftriaxone should be used unless there is a clear history of penicillin anaphylaxis.

In this case, discuss antibiotics with specialists in infectious diseases and/or microbiology.

Alternatives include vancomycin (poor CSF penetration; Gram-positive organisms only), aminoglycosides (poor CSF penetration) or chloramphenicol (good CSF penetration). All are more likely to be used in secondary care.

Chemoprophylaxis
In confirmed MCD and Hib, all household contacts within the past seven days should be offered chemoprophylaxis.

Family members (same household) should be treated in secondary care; other potential contacts should be referred or discussed with public health specialists.6

If contacts are unimmunised children, meningococcal C, pneumococcal conjugate vaccine and/or Hib vaccine should be offered.

Hib chemoprophylaxis

  • Children and adults: rifampicin once daily 20mg/kg oral (maximum dose 600mg/dose) for four days.

MCD chemoprophylaxis

  • Children: rifampicin twice daily 10mg/kg oral (maximum dose 600mg/dose) for two days.
  • Adults: ciprofloxacin 500mg one dose.
  • Pregnant women: ceftriaxone 250mg IM one dose.
Duration of treatment
  • MCD Seven days
  • Strep pneumoniae 10-14 days
  • Hib Seven days
  • Group B streptococcus 14-21 days
  • Gram-negative bacilli 21 days
  • Listeria monocytogenes 21 days or longer
  • If no organism is identified, it is usual to treat the patient for a minimum of 10-14 days.
  • Shorter courses have been advocated in the past, but are not routinely employed.

Section 4: Prognosis

Death from meningitis in children in most developed countries is uncommon; it ranges from <1% (MCD without sepsis) to >10% (pneumococcal disease). However, mortality rates are higher if the diagnosis is delayed or missed, if experienced clinicians were not involved and if aggressive treatment is not instigated early.7

Average complication rates in all forms of meningitis include:

  • Learning difficulties (7.5%).
  • Neurodisabilities (8.1%).
  • Seizure disorders (7.3%); poorer prognosis associated with focal, prolonged or late-onset seizures.
  • Hearing loss (25.8%).
  • Visual disorders (13.7%).
  • Speech and/or language problems (15.6%).
  • Behavioural problems (11.9%).

All children who have had meningitis require follow-up to monitor outcomes and progress. All such patients should have a hearing assessment soon after discharge, which should be repeated if there are concerns about hearing or speech for which no other cause is found.

Early referral for cochlear implant assessment is vital in patients with severe hearing loss, before the inner ear ossifies.

Disabilities
Disability rates in meningitis survivors vary, depending on the causative organism.

For MCD survivors, rates for no disability versus severe disability were 60.7% and 2.9%, respectively, compared to 21.9% and 25% for Gram-negative meningitis.8

Children who have had recurrent episodes of meningitis or MCD, meningitis caused by an organism they have been vaccinated against, or an unusual meningococcal serotype should be referred for immune system assessment, particularly looking at complement function.5

Patients with complement deficiency are rare, but have a higher mortality rate.

Section 5: Case study

In primary care, you see a five-year-old girl with fever >38 degsC, possible neck stiffness but has tonsillitis (red with pus), with a rash over her trunk, some of which blanches but a few other spots do not disappear under a glass. What should you do?

She needs careful assessment of her level of consciousness (alert, talking, response to pain or unconscious), circulation (capillary refill time, pulse, BP) and rash (blanching or not).

There is a high probability she has MCD, septicaemia and meningitis. Patients with MCD can have signs of other viral infections, such as tonsillitis or viral lower respiratory tract infection, and classic signs of MCD (unwell, non-blanching rash, fever and neck stiffness).

The child should be given IM penicillin and taken to hospital as an emergency case.

She did have MCD, received seven days of ceftriaxone and made a full recovery. The girl's aunt then comes to see you, demanding prophylaxis for her children, who played with their cousin six days ago.

MCD is distressing for relatives and contacts. There is little evidence that prophylaxis prevents secondary cases (grade C).9 I have seen cases where some contacts have been given prophylaxis by one GP, but others, at a different surgery, have been refused it, causing anxiety.

The hospital case may not have been confirmed at this stage. It could be a case of a petechial rash secondary to a viral illness, rather than MCD.

The correct answer to this request is to refer the aunt's details to public health, who will arrange prophylaxis if needed. Secondary care will have informed public health if they think they have a probable or confirmed MCD or Hib case.

Secondary care will prescribe prophylaxis for household contacts. Other contacts are risk- assessed by public health, who arrange prophylaxis if needed.

Section 6: Evidence base

Clinical trials

  • Thompson MJ, Ninis N, Perera R et al. Clinical recognition of meningococcal disease in children and adolescents. Lancet 2006; 367: 397-403.

There is growing evidence that delay in the recognition and aggressive management of MCD is significantly associated with poorer outcomes and death.

  • Bedford H, de Louvois J, Halket S et al. Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ 2001; 323: 533.

There is little research into the outcomes of children with meningitis, but this paper is very informative.

Guidelines
NICE and SIGN have published comprehensive guidelines, although their evidence and references can be difficult to find.

A 45-page practical plan for the management of all children with suspected meningitis, from clinical history and diagnosis to management and follow-up.

  • NICE. Quick reference guide. Bacterial meningitis and meningococcal septicaemia. Management of bacterial meningitis and meningococcal septicaemia in children and young people younger than 16 years in primary and secondary care. London, NICE, September 2010. Pre-hospital management of suspected bacterial meningitis and meningococcal septicaemia is covered section 1; 1.2 page 15.

This quick reference guide includes an algorithm covering pre-hospital management of patients with meningococcal disease and bacterial meningitis (page 10).

This information is similar to the NICE guidance, but only covers MCD.


The Meningitis Research Foundation

Online

  • The Health Protection Agency website contains epidemiological data, both current and historical, for numerous illnesses including all forms of meningitis, MCD, Hib and pneumococcal diseases in England. www.hpa.org.uk

Meningitis can be a devastating illness for families. Support and advice for the parents and relatives of children who have had meningitis are available from charities, including:

Reflect on this article and add notes to your CPD Organiser on MIMS Learning

CPD IMPACT: EARN MORE CREDITS

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Organise a roadshow with the help of your patient participation group to educate parents about meningitis.
  • Perform a case review of all meningitis cases in your practice in the past five years and present the findings to your colleagues.
  • Organise a practice training day on meningitis, including informing the receptionists about how to recognise a sick child in the waiting room.

References
1. HPA. Statutory Notifications of Infectious Diseases (Noids) England and Wales Annual totals - 1982 to 1990 for diseases notifiable under Health Protection Regulations 2010. www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1251473364307

2. HPA. Laboratory reports of Haemophilus influenzae type b infection by age group and quarter: England and Wales: 1990-2010. www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/HaemophilusInfluen zaeTypeB/EpidemiologicalData/haem_DataLabAgeQtr/

3. HPA. Laboratory confirmed cases of serogroup C disease only by age and epidemiological year, England and Wales 1998-99 to 2009-10. www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb_C/1234859709051

4. HPA. Invasive Pneumococcal Disease (IPD) in England & Wales after 7 Valent Conjugate Vaccine (PCV7). Potential impact of 10 and 13 valent vaccines. www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Pneumococcal/Epide miologicalDataPneumococcal/

5. NICE. The management of bacterial meningitis and meningococcal septicaemia in children and young people younger than 16 years in primary and secondary care. London, NICE, 2010.

6. Immunisation against infectious disease. The Green Book, 2006. Chapter 22: Meningococcal, updated 26 March 2012.

7. Ninis N, Phillips C, Bailey L et al. The role of healthcare delivery in the outcome of meningococcal disease in children: case-control study of fatal and non-fatal cases. BMJ 2005; 330: 1475-8.

8. Bedford H, de Louvois J, Halket S et al. Meningitis in infancy in England and Wales: follow up at age 5 years, BMJ 2001; 323: 533.

9. HPA. Guidance for public health management of meningococcal disease in the UK. www.hpa.org.uk/ web/HPAweb&Page& HPAwebAutoList Name/Page/1201094595231

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